Robert E. Weinstein

Tissue ferritin concentration in carcinoma of the breast

Ferritin concentration was measured in cytosol extracts of 44 mammary carcinomas and 14 benign breast tissues. A six‐fold difference was observed (mean, 364.6 ± 223.3 ng/mcp in malignant tissue versus mean, 60.2 ± 42.1 ng/mcp in benign tissue P < 0.001). Thirty‐five malignant tissue specimens were reviewed independently by a pathologist without knowledge of their ferritin contents. Higher concentrations of ferritin were present in malignancies with greater degrees of epithelial proliferation and plemorphism suggesting the malignant epithelium as the major site of the increased ferritin. There was no correlation between desmoplastic reaction within the tumors or inflammation within or adjacent to the tumors and ferritin concentration. Ferritin in breast tissue may be important as a marker of neoplasia, a source of elevated serum ferritin, an indicator of clinical prognosis or an immunosuppressive substance.

Tissue ferritin concentration and prognosis in carcinoma of the breast

SummarySeven year follow-up data were available on 36 of 40 breast carcinoma patients in whom breast tissue ferritin concentrations at the time of surgery were known. 18 patients were alive and free of recurrence or second tumor (Group 1) and 11 died with breast cancer (Group 2). Patients with lower tissue ferritin concentrations defined as < 319 ng/mcp (nanograms of ferritin/milligram of cytosol protein) were at reduced risk: 86% of patients with low tissue ferritin concentration survived free of recurrence or second tumor vs. 40% of patients with high tissue ferritin concentration (P = 0.0056). Mean breast carcinoma tissue ferritin concentration was 295 ± 52 ng/mcp in Group 1 and 444 ± 55 ng/mcp in Group 2 (P = 0.036).Lymph node involvement was predictive of mortality from breast carcinoma (P = 0.0003), but did not correlate with mean tissue ferritin concentration (P = 0.082). 10/10 (100%) patients who had both low tissue ferritin concentration and absence of lymph node involvement were in Group 1.The correlation of breast tissue ferritin concentration with histopathologic dedifferentiation and with prognosis suggests tumor tissue ferritin as a marker of malignant potential.

Ferritin Content in Human Cancerous and Noncancerous Colonic Tissue

Tumor tissue samples from 25 patients with adenocarcinoma of the colon, twelve related samples of normal colons as well as five serum specimens from the same patients were analyzed for ferritin. The average ferritin content of the tumor tissue was 788 ng/mcp with a range of 47-1,745 ng/mcp. The average ferritin content of normal colon mucosa was 115 ng/mcp with a range of 32-230 ng/mcp. Two specimens of metastatic colon cancer taken from the retroperitoneal space and liver, respectively, contained 3,867 and 2,827 ng/mcp of ferritin. The ferritin content of the tumor tissue was higher than that of the normal colon in 8 of 9 patients who had specimens obtained from both sites. The amount of ferritin found in tumor tissue was independent of sex, age, and the site of the original tumor. This study shows that the ferritin content of colon neoplasms is elevated and indicates that the tumor tissue may be the direct source of elevated serum levels of ferritin previously observed in cancer patients.

Altered cerebral dominance in an atopic population

Handedness was assessed in 853 subjects, 424 from an allergy office practice and 429 from a health screening clinic, using a modified Oldfield Handedness Inventory. Subjects also responded to a survey ascertaining both personal and family histories of allergy-related problems and left-handedness. A significant left-handed shift in mean laterality quotient and an increased incidence of left-handedness was found in participants from the allergy office and in subjects who considered themselves to be affected by allergy, allergic rhinitis, and/or asthma. Controlling for nonatopic responders from the allergy office and possibly atopic responders from the health screening clinic, mean laterality quotients were 66.4 +/- 51.6 vs 79.4 +/- 42.1 (p less than .001) and the incidence of left-handedness was 12.1% vs 6.8% (p less than .05). Mean laterality quotient of 125 asthmatics was 65.1 +/- 54.0, and 16 (12.8%) were left-handed. The mean percentage of left-handed children of 79 asthmatic parents was found to be increased: 16.7 +/- 26.3% vs 10.3 +/- 21.2% of children of 198 nonatopic parents (p less than .02). This was attributable to left-handed children of asthmatic women, 18.6 +/- 29.0% (p less than .01), but not asthmatic men. Both autonomic neurologic dysfunction and disordered immunoregulation typify atopic disease. Our results can be interpreted to reflect this duality and lend support to Geshwinds hypothesis of a relationship between cerebral dominance and immunologic set resulting from common developmental influences.

Decreased adrenal sex steroid levels in the absence of glucocorticoid suppression in postmenopausal asthmatic women

BACKGROUND AND AIM Reduction of serum sex steroid levels has been reported to occur after the administration of beta-adrenergic medication. In that beta-adrenergic blockade is a central pathophysiologic feature of asthma, this study was done to explore the possibility of hormonal alteration in asthma. METHODS Sex steroids obtained from 22 postmenopausal asthmatic and 22 age-matched, postmenopausal, nonasthmatic women were assayed. No subject had received estrogens, progestins, or oral corticosteroids for 120 days before the study. RESULTS Mean dehydroepiandrosterone sulfate (DHEAS; p < 0.002), dehydroepiandrosterone (DHEA; p < 0.03), estradiol (p < 0.02), and estrone (p < 0.02) levels were lower in asthmatic patients compared with nonasthmatic subjects. Results could not be accounted for by current medication. Patients with asthma demonstrated no decrease in 17-hydroxyprogesterone or cortisol compared with nonasthmatic subjects, limiting findings to the delta 5, and not the delta 4, steroidogenic pathway. In a second phase of the study, DHEAS was measured before and after 3 days of oral beta-agonist stimulation in eight postmenopausal asthmatic women. Serum DHEAS concentration increased in eight of eight subjects, from a mean of 28.6 +/- 19.9 micrograms/dl (mean +/- SD) to 40.7 +/- 24.8 micrograms/dl (p = 0.002). Serum cortisol concentration was unchanged. CONCLUSION The results indicate that postmenopausal asthmatic women have lower serum levels of adrenally derived sex steroids than their nonasthmatic peers and that this anomaly may be ameliorated by adrenergic stimulation.